Visualizing genetic constraints

Principal Components Analysis (PCA) is a common way to study the sources of variation in a high-dimensional data set. Typically, the leading principal components are used to understand the variation in the data or to reduce the dimension of the data for subsequent analysis. The remaining principal components are ignored since they explain little of the variation in the data. However, evolutionary biologists gain important insights from these low variation directions. Specifically, they are interested in directions of low genetic variability that are biologically interpretable. These directions are called genetic constraints and indicate directions in which a trait cannot evolve through selection. Here, we propose studying the subspace spanned by low variance principal components by determining vectors in this subspace that are simplest. Our method and accompanying graphical displays enhance the biologist's ability to visualize the subspace and identify interpretable directions of low genetic variability that align with simple directions.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS603 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Longitudinal Analysis of Antibody Responses to Trachoma Antigens Before and After Mass Drug Administration.

Blinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drug administration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment. Dried blood spots and ocular swabs were collected with parental consent from 264 1-6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots. Baseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed. Data presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs

DoD-GEIS Rift Valley Fever Monitoring and Prediction System as a Tool for Defense and US Diplomacy

Over the last 10 years the Armed Forces Health Surveillance Center's Global Emerging Infections Surveillance and Response System (GEIS) partnering with NASA'S Goddard Space Flight Center and USDA's USDA-Center for Medical, Agricultural & Veterinary Entomology established and have operated the Rift Valley fever Monitoring and Prediction System to monitor, predict and assess the risk of Rift Valley fever outbreaks and other vector-borne diseases over Africa and the Middle East. This system is built on legacy DoD basic research conducted by Walter Reed Army Institute of Research overseas laboratory (US Army Medical Research Unit-Kenya) and the operational satellite environmental monitoring by NASA GSFC. Over the last 10 years of operation the system has predicted outbreaks of Rift Valley fever in the Horn of Africa, Sudan, South Africa and Mauritania. The ability to predict an outbreak several months before it occurs provides early warning to protect deployed forces, enhance public health in concerned countries and is a valuable tool use.d by the State Department in US Diplomacy. At the international level the system has been used by the Food and Agricultural Organization (FAD) and the World Health Organization (WHO) to support their monitoring, surveillance and response programs in the livestock sector and human health. This project is a successful testament of leveraging resources of different federal agencies to achieve objectives of force health protection, health and diplomacy

Use of the X-Band Radar to Support the Detection of In-Flight Icing Hazards by the NASA Icing Remote Sensing System

The Alliance Icing Research Study-II (AIRS-II) field program was conducted near Montreal, Canada during the winter of 2003. The NASA Icing Remote Detection System (NIRSS) was deployed to detect in-flight icing hazards and consisted of a vertically pointing multichannel radiometer, a ceilometer and an x-band cloud radar. The radiometer was used to derive atmospheric temperature soundings and integrated liquid water, while the ceilometer and radar were used only to define cloud boundaries. The purpose of this study is to show that the radar reflectivity profiles from AIRS-II case studies could be used to provide a qualitative icing hazard

Epidemic spread of adenovirus type 4-associated acute respiratory disease between U.S. Army installations.

A large outbreak of adenovirus type 4-associated acute respiratory disease (ARD) occurred at Fort Jackson, South Carolina, in 1997. A laboratory-based ARD surveillance program was initiated at Fort Gordon, Georgia, where advanced individual training was heavily populated with Fort Jackson soldiers. Adenovirus type 4 was isolated from 50% of 147 trainees hospitalized with ARD. Most (88%) introduced cases were in trainees from Fort Jackson

The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel.

BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010)

Quantification of HIV-1 RNA Among Men Who Have Sex With Men Using an At-Home Self-Collected Dried Blood Spot Specimen: Feasibility Study

Background: Suboptimal antiretroviral therapy (ART) adherence and disengagement in care present significant public health challenges because of the increased probability of HIV transmission. In the United States, men who have sex with men (MSM) continue to be disproportionately affected by HIV, highlighting a critical need to engage high-risk MSM living with HIV who are not engaged or retained in care. Objective: The aim of the study was to assess the feasibility of at-home blood self-collection and laboratory quantification of HIV-1 RNA viral load (VL) to report laboratory-based VL outcomes and compare self-reported and laboratory-reported VL Methods: Between 2016 and 2017, 766 US HIV-positive MSM enrolled in a Web-based behavioral intervention were invited to participate in an at-home dried blood spot (DBS) collection study using HemaSpot-HF kits (Spot On Sciences, Inc, Austin, TX) for laboratory-quantified VL. Results: Of those invited to participate, 72.3% (554/766) enrolled in the DBS study. Most (79.2%, 439/554) men enrolled reported attempting to collect their blood, 75.5% (418/554) of participants mailed a DBS specimen to the research laboratory, and 60.8% (337/554) had an adequate blood sample for VL testing. Of the 337 specimens tested for VL by the laboratory, 52.5% (177/337) had detectable VL (median: 3508 copies/mL; range: 851-1,202,265 copies/mL). Most men (83.9%, 135/161) who returned a DBS specimen with laboratory-quantified detectable VL self-reported an undetectable VL during their last clinical visit. Conclusions: Home collection of DBS samples from HIV-positive MSM is feasible and has the potential to support clinical VL monitoring. Discrepant laboratory HIV-1 RNA values and self-reported VL indicate a need to address perceived VL status, especially in the era of treatment as prevention. Most participants were willing to use an at-home DBS kit in the future, signaling an opportunity to engage high-risk MSM in long-term HIV care activities

Herpes Simplex Virus Type 2 Seroprevalence and Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young African-American Women

For decades reproductive tract infections (RTIs) have been hypothesized to play a role in uterine fibroid development. The few previous studies conducted used self-reported history of RTIs and had inconsistent findings. We investigated this hypothesis further using serological analysis, an immunological measure of past exposure. We focused on herpes simplex virus type 2 (HSV-2) because prior published data have suggested a possible association with fibroids, and serology for HSV-2 is much more sensitive than self-report. We used cross-sectional enrollment data from African-American women enrolled in a prospective study of fibroid incidence and growth (recruited 2010–2012) in the Detroit, Michigan, area. The women were aged 23–34 years and were screened for fibroids using a standardized ultrasound examination at their enrollment. Age- and multivariable-adjusted logistic regression models were used to estimate odds ratios. Of 1,696 participants, 1,658 had blood samples and HSV-2 serology results; 22% of participants with serology results had fibroids. There was no significant association between HSV-2 seropositivity and the presence of fibroids (multivariable-adjusted odds ratio = 0.94, 95% confidence interval: 0.73, 1.20), nor were there any associations with size of the largest fibroid, number of fibroids, or total fibroid volume. Our data provide no evidence for an influence of HSV-2 exposure on fibroid risk in young African-American women. Further study of other serologically measured RTIs is warranted